All about Folate and Folic Acid

Folate deficiency is the most common vitamin deficiency in developed countries, contributing to serious health problems such as neural tube defects (NTDs), megaloblastic anemia, digestive disorders, cardiovascular disease, mood disorders, and others. Using supplements with folic acid may reduce the risks associated with folate deficiency.

What are folates?

In 1941, Esmond Snell, one of the most famous biochemists of the 20th century, isolated folate from four tons of spinach leaves. That’s a lot of spinach!

Folates are a group of water-soluble compounds that have a chemical structure and nutritional activity similar to folic acid.

Folate and folic acid are sometimes confused. What is the difference?

Folate occurs naturally in food. Folic acid is synthesized in the laboratory and is found in food supplements and fortified foods. (It is rarely found in natural foods.)

Interestingly, folic acid is better absorbed than folate found in food. This is one case where the “processed” version might actually be an idea above the natural!

Structure of folates

What do folates do?

Folates help with many processes in our bodies. They can:

  • Improve the efficiency of DNA repair & copying.
  • Help with RNA synthesis.
  • Help the interpretation of amino acids (including the conversion of homocysteine).
  • To protect us from free radicals and oxidation.

The conclusion is that they help us to be healthy.

The role of Folate in our health


Folate deficiency is the most common vitamin deficiency in developed countries. Deficiency may result from low intake, malabsorption and/or alcoholism.

Folate deficiency can lead to neural tube defects (NTDs), stunted growth, megaloblastic anemia, weight loss, eating disorders, leukopenia, thrombocytopenia, tongue/mouth cracking/redness, diarrhea, cancer, cardiovascular disease, and behavioral changes.


Red blood cells are produced in the bone marrow. Red blood cell production requires a high rate of cell division. Without enough folate, cell division and protein synthesis are limited, contributing to large, abnormal and incomplete red blood cells called megaloblasts. (This is why the disease is called megaloblastic anemia)

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However, folate and vitamin B12 are interdependent and megaloblastic anemia can also be caused by a lack of B12. High doses of folic acid in supplement form can mask malignant anemia caused by a lack of vitamin B12.


In the 1960s, researchers discovered folate dependence as a major cause of preventable neural tube defects (NTDs). Neural tube = embryonic precursor of the brain and spinal cord. When the neural tube fails to close during pregnancy, this results in the form of neural tube defects (NTDs). DVTs are the second most common cause of serious birth defects. Normally, the neural tube closes 28 days after conception.

Pregnancy doubles the need for folate. Low folate intake before and during pregnancy can lead to preterm birth, low birth weight and LBW.

Folic acid supplementation before conception can reduce the DHT by about 70%. This important discovery has led to government recommendations for pregnant women. Since then, foods fortified with folate have significantly reduced the incidence of DNT (between 19 and 49%).

However, not all DNTs can be prevented with dietary supplements. Plus, a high dose of folic acid late in pregnancy has been associated with asthma in the embryo.

Because breast milk provides folate to the newborn, the mother’s needs continue to be high during breastfeeding. Breastfed babies have a better folate status than those fed artificial milk.

Neural tube defects
Spina bifida is one of the most common DST


Low blood folate levels are associated with higher blood homocysteine levels. Higher levels of homocysteine in the body are associated with cardiovascular disease.

Using folic acid supplements may not always lower homocysteine levels in the body. However, it still seems to protect the heart (probably because of the reduction of oxidative damage). High blood homocysteine is associated with DNT, oral fissures, congenital heart defects, atherosclerosis, Down syndrome, Alzheimer’s disease, depression, breast cancer, and diabetes. Why? High levels of homocysteine in the body can reduce the function of several important components. When these components are not working properly high levels of oxidative stress, inflammation and blood vessel dysfunction occur.


High levels of homocysteine in the body are associated with depression. Not only that, but high levels of depression have been found in those who lack folate.

This is probably related to the involvement of folate in the metabolism and processing of various neurotransmitters that regulate mood (e.g., dopamine, serotonin).


Folate may protect against cancer (colon cancer in particular).

Folates are required in methylation reactions. DNA methylation appears to be valuable in preventing cancer.

MTHFR (Methylene-tetra-hydro-folate reductase)

MTHFR is an enzyme required for homocysteine metabolism. Normally MTHFR is needed to balance blood levels of folate and homocysteine.

However, some people have a genetic variant of MTHFR that alters its action, leaving less folate and more homocysteine to build up in the body. People with this particular variant probably need to consume more folate.

In mothers with this variant, extremely high levels of homocysteine can occur. This can be a risk factor for having a child with Down syndrome. At the same time, it is not clear whether folic acid supplements can compensate for this. While researchers believed that mandatory folic acid fortification in America would reduce the manifestation of Down syndrome, this has not happened.

The data are not definitive, but it seems that different genetic variations may play a role, along with genetic/environmental interactions. In other words, at the moment, we cannot draw concrete conclusions.

However, many experts suggest that those with MTHFR deficiency (40% of the population carries these genes, and 10% show symptoms) supplement themselves with higher doses of folic acid or folinic acid (a slightly modified form of folate) using supplements.


If someone eats an adequate and varied diet, presumably they can get enough folate. However, folates are unstable and suffer losses during food processing. Folates in animal foods vary because of the animal’s diet, geographical location and season. Some reports indicate that 30-90% of the folate can be lost from farm to plate.

Methods for assessing folate in foods appear to be inconsistent. The bioavailability of folates ranges from 40-70%.

Foods rich in folate include beans, peas, green leafy vegetables, asparagus, organ meats, broccoli, Brussels sprouts, peanuts, tomato juice, bananas, papaya, and citrus fruits. The microflora of the human colon can produce folate, which can then be absorbed into the body through the colon wall.


Dietary fortification with folic acid was allowed in America in 1996 and introduced in 1998, providing 140 mcg per 100 grams of food.

Some speculate that fortification is not wise – due to some associations between folic acid and subclinical cancer and other developments of ill health. These days, however, to avoid this folic acid fortification you need to use 100% unprocessed, unrefined whole grains.

Absorption of Folate

Most folate is absorbed in the small intestine (the first part of the small intestine, to be exact). Once the folates enter circulation, the cellular example starts after a few minutes.

The body can store about 20-70 mg of folate in the liver. Folate is eliminated from the liver by bile. (While fasting, bile is our main source of folate). They leave the body through the urine and faeces, usually not as intact folate but as a broken down product. The daily round is about 90 mcg.

Some foods contain substances that affect folate absorption.

For example, dairy products contain folate binding protein (FBP). Heat treatment of the milk destroys the FSP (and destroys some of the folate. Fermented milk contains higher levels of folate (compared to pasteurised milk). The whey portion contains the most of the FSP. Therefore, cheese contains less FSP because a lot of whey is separated during processing.

FSP can work in the mammary gland to trap folate from the blood plasma in the milk. It may also aid in the digestion of folate, acting as a type of intestinal gatekeeper, preventing bacteria from consuming the folate.

Catechins and polyphenols (found in tea, cocoa, wine and other plant foods) can suppress the action of folate. Daily coffee consumption in China is associated with a higher risk of HTN.

The Folic Acid Equivalency in Diets (FAD) was developed to cater for the differences in absorption between folic acid and naturally occurring folate. 1 RFD = 1 mcg dietary folate = 0.6 mcg folic acid from supplements and fortified foods.

Folate status

The main indicator of long term (~100 days) folate status is the concentration of folate in red blood cells. This measurement will not show an emergency failure. This test does not require fasting overnight.

Simply measuring blood folate levels cannot indicate long-term folate status with certainty. However, measuring blood folate levels after an overnight fast can help catch an emerging deficiency.

High blood homocysteine levels may also be an early indicator of folate deficiency.

If liver stores are full and no additional folate is taken, signs of failure will develop within 3-6 months. The first signs of failure include megaloblastic anemia, depression, insomnia, cognitive dysfunction, dementia, and mood swings.

Those who overindulge in alcohol are at risk of folate deficiency.

Summary and recommendations

With modern food processing, it takes a focused effort to reach our folate intake requirements from food alone.

Most adults should try to take about 400 mcg/day of RFD (or 240 mcg/day of folic acid). To make sure you are taking enough, feel free to use a nutritional supplement.

The following populations are likely to need increased folate and/or folic acid intake in the form of supplements:

  • Anyone with malabsorptive disease (inflammatory bowel disease, celiac disease, etc.)
  • These cMTHP option (check with your doc.
  • Woman who may be pregnant (consume at least 600 mcg of folic acid per day).
  • Breastfeeding woman (consume at least 600 mcg of folic acid per day. Use a dietary supplement to reach these goals)
  • Anyone with elevated blood homocysteine levels. To control homocysteine, try to consume at least 400 mcg of folic acid per day. Use a nutritional supplement to reach these intakes. Also, take enough vitamin B12 and vitamin B6. Discuss with your doctor to have your blood levels tested.

Saturation is not a consideration unless you eat a lot of folate fortified foods along with folic acid supplements. Avoid consuming more than 1000 mcg/day of folic acid in the form of supplements (or folic acid from folate-fortified foods).

Additional credit

  • Methotrexate is a drug used to treat rheumatoid arthritis, psoriasis, and some cancers. It is a folate antagonist.
  • Why might you want to fight folates? Well, since folates affect DNA and RNA, they can also affect disease progression. This can be in positive and negative aspects.
  • Medicinal sulfazin interferes with the absorption of folate.
  • NSAIDs (non-steroidal anti-inflammatory drugs, for example Ibuprofen, Aspirin) can alter the action of folate.
  • Some anticonvulsant medications can reduce folate uptake in the body.
  • Folates play a role in the bioavailability of nitric oxide.
  • Smoking can disable folate.
  • Certain strains of probiotics can produce folate.
  • Northern China have several vegetables rich in folate. Folic acid interventions in this region have shown solid benefits.
  • Low maternal vitamin B12 levels are associated with a high risk of DNT.
  • Betaine can also help lower blood levels ofhomocysteine.
  • The bioavailability of folic acid from tablets and soft gel capsules appears to be similar.
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